Philipp Röntgen

Abstract Aims Peripartum cardiomyopathy (PPCM) is a major cause of acute heart failure in the peripartum period and considered potentially life threatening. While many aspects of its clinical profiles have been frequently reported, functional analysis, in particular of the right ventricle, and tissue characterization by cardiovascular magnetic resonance (CMR) imaging have been only sporadically described. The aim of the present study was to analyse pathological alterations and their prognostic relevance found in CMR imaging of patients newly diagnosed with PPCM. Methods and results In this multicenter study 34 patients with confirmed PPCM underwent CMR imaging at the time of diagnosis and at 5±1months follow-up. Cine imaging of PPCM patients showed moderate to severe reduction of systolic left ventricular (LV) function (mean LVEF: 29.7±12.8%). In 35% of the patients right ventricular (RV) systolic function was also reduced with a mean RVEF of 42.9±13.9%. Dilatation of the LV was observed in 91% (mean LV-EDV/BSA 128.5±32.1mL/m2), and dilatation of the RV was present in 24% (mean RV-EDV/BSA 87.4±18.5mL/m2) of the patients. Focal non-ischemic late gadolinium enhancement (LGE) was visible in 71%, and regional wall motion abnormalities were evident in 88% of the patients. LGE and wall motion abnormalities were predominantly located in the anteroseptal and basal to midventricular segments. RV dysfunction at baseline was associated with reduced probability of full cardiac recovery at 5±1months follow-up. Conclusions Besides LV systolic dysfunction, RV dysfunction and dilatation are observed in about one third of PPCM patients at the time of diagnosis. RV dysfunction is associated with unfavourable outcome. A distinct pattern of LV wall motion abnormalities and myocardial scar is evident in most PPCM patients. The present study may help to establish a set of CMR criteria suitable for diagnosis in patients with suspected PPCM and may add further knowledge to the pathology of the disease.

Background: Limited progress has been made in the management of cardiogenic shock (CS). Morbidity and mortality of refractory CS remain high. The effects of mechanical circulatory support (MCS) are promising, although many aspects are elusive. We evaluated efficacy and safety of early combined MCS (Impella microaxial pump + venoarterial extracorporeal membrane oxygenation [VA-ECMO]) in refractory CS and aimed to determine factors for decision-making in combined MCS. Methods and Results: We analyzed 69 consecutive patients with refractory CS from our registry requiring combined MCS. In 12 cases, therapy was actively withdrawn according to patient’s will. Patients were severely sick (Survival After Venoarterial ECMO score mean±SD, –8.9±4.4) predicting 30% in-hospital survival; ventilation 94%, dialysis 56%. Impella pumps and VA-ECMO were combined early (duration of combined MCS: median 94 hours; interquartile range, 49–150 hours). Early MCS escalation stabilized patients rapidly, reducing number and doses of catecholamines ( P <0.05 versus baseline) while hemodynamics improved. Reflecting an improved microcirculation, lactate levels normalized within 24 hours ( P <0.05 versus baseline). Despite refractory CS and disease severity, survival was favorable (on MCS 61%, 30 days 49%, 6 months 40%). In multivariate Cox-regression, duration of shock-to-first device (hours, hazard ratio, 1.05 [95% CI, 1.01–1.08]; P =0.007) and lactate levels after 12 hours of MCS (hazard ratio, 1.28 [95% CI, 1.09–1.51]; P =0.002) independently predicted survival. Additional right ventricular failure predisposed to futility (hazard ratio, 8.48 [95% CI, 1.85–38.91]; P =0.006). Conclusions: The early and consequent combination of MCS by Impella microaxial pumps and VA-ECMO enables stabilization and may rescue high-risk patients with refractory CS at low overall risk. Independent predictors of survival may guide prognostication, decision-making, and allocation of medical resources.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is an idiopathic heart disease that develops in the last month of pregnancy and/or the first months following delivery in previously healthy women and may lead to acute heart failure. A cleaved fragment of the nursing hormone prolactin is considered essential in the pathophysiology of PPCM. To date, no specific therapy has been tested for PPCM in a randomized controlled trial of adequate size. AIMS: The purpose of this trial is to investigate the safety of the dopamin-D2-receptor agonist bromocriptine and its effects on left ventricular (LV) function in women with PPCM. METHODS: This is an 11 center German trial with a prospective randomized controlled open-label design. The trial enrolls females with newly diagnosed PPCM according to European Society of Cardiology criteria with a LV ejection fraction (LVEF) <35 %. Patients are randomized 1:1 to either best supportive care (BSC) including standard heart failure therapy plus 8 weeks of bromocriptine therapy (2.5 mg b.i.d. for 14 days and 2.5 mg q.d. from day 15 to 56) or to BSC plus 1 week of low-dose bromocriptine (2.5 mg q.d.) with anticoagulant therapy at a prophylactic dose administered during the period of bromocriptine treatment in both groups. The primary endpoint is change in LVEF from baseline to 6 months follow-up as assessed by cardiac magnetic resonance imaging (or echocardiography if CMR is not tolerated). The secondary endpoints are hospitalization for worsening heart failure, heart transplantation, and all-cause mortality during follow-up or a combination of these endpoints. A total of 60 patients will be recruited (including 6 potential dropouts) giving a power of 0.9 for an expected LVEF change of 10.8 % between treatment groups at 6 months. PERSPECTIVE: This trial will provide important knowledge on potential benefits and safety of prolonged inhibition of prolactin release with bromocriptine in addition to standard heart failure therapy in newly diagnosed PPCM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00998556.

Proinflammatory cytokines produced by monocytes, like Interleukin-6 (IL-6), Interleukin-8 (IL-8), and tumor necrosis factor (TNF-alpha) are known for their pivotal role in the initiation of the inflammatory response following cardiopulmonary bypass (CPB). Catecholamines like epinephrine (Epi) and norepinephrine (Nor) are often necessary to stabilize the cardiac function in the early postoperative period and may influence the cytokine expression in monocytes. In this study we investigated the effects of Epi and Nor on IL-6, IL-8 and TNF-alpha expression in human monocytes stimulated with lipopolysaccharide (LPS) in whole blood, analyzed intracellularly by flow cytometry. Kinetics of intracellular proinflammatory cytokine production and LPS ED(50) were obtained. To simulate different stages of inflammation in vivo, varying concentrations of LPS (0.2 ng/ml, 1 ng/ml and 10 ng/ml) were used for stimulation. After a stimulation with LPS TNF-alpha was the first produced cytokine, followed by IL-8 and IL-6. All cytokines peaked from 3 h to 6 h. Epi and Nor had comparable effects on the expression of IL-6, IL-8 and TNF-a in monocytes. Both inhibited IL-6 and TNF-alpha expression in a concentration dependent manner whereas IL-8 expression remained unchanged. We conclude that monocytes are targets for Epi and Nor concerning their cytokine expression. The inhibiting effects of Nor and Epi were almost identical for all cytokines. Cytokine expression was affected most at low LPS concentrations.